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Intact-cell MALDI-ToF mass spectrometry for the authentication of drug-adapted cancer cell lines

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Povey, Jane F., Saintas, Emily, Aderemi, Adewale V., Rothweiler, Florian, Zehner, Richard, Dirks, Wilhelm G., Cinatl, Jindrich, Racher, Andrew J. +3 more·2019·Cells

Abstract

The use of cell lines in research can be affected by cell line misidentification. Short tandem repeat (STR) analysis is an effective method, and the gold standard, for the identification of the genetic origin of a cell line, but methods that allow the discrimination between cell lines of the same genetic origin are lacking. Here, we use intact cell MALDI-ToF mass spectrometry analysis, routinely used for the identification of bacteria in clinical diagnostic procedures, for the authentication of a set of cell lines consisting of three parental neuroblastoma cell lines (IMR-5, IMR-32 and UKF-NB-3) and eleven drug-adapted sublines. Principal component analysis (PCA) of intact-cell MALDI-ToF mass spectrometry data revealed clear differences between most, but not all, of the investigated cell lines. Mass spectrometry whole-cell fingerprints enabled the separation of IMR-32 and its clonal subline IMR-5. Sublines that had been adapted to closely related drugs, for example, the cisplatin- and oxaliplatin-resistant UKF-NB-3 sublines and the vincristine- and vinblastine-adapted IMR-5 sublines, also displayed clearly distinctive patterns. In conclusion, intact whole-cell MALDI-ToF mass spectrometry has the potential to be further developed into an authentication method for mammalian cells of a common genetic origin.

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  • Intact cell MALDI-ToF mass spectrometry has been successfully harnessed to distinguish drug-adapted sublineages from their parental lines.

    “Intact cell MALDI-ToF mass spectrometry-normally used for the clinical recognition of bacteria-has been successfully harnessed to distinguish drug-adapted sublineages from their parental lines [8].”

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  1. [1]Lucey B.P. Nelson-Rees W.A. Hutchins G.M. Henrietta Lacks, HeLa cells, and cell culture contamination Arch. Pathol. Lab. Med. 2009 133 1463 1467 19722756
  2. [3]Scherer W.F. Syverton J.T. Gey G.O. Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix J. Exp. Med. 1953 97 695 710 10.1084/jem.97.5.695 13052828 PMC2136303 · DOI · Paper page
  3. [4]Defendi V. Billingham R.E. Silvers W.K. Moorhead P. Immunological and karyological criteria for identification of cell lines J. Natl. Cancer Inst. 1960 25 359 385 13815376
  4. [5]Brand K.G. Syverton J.T. Results of species-specific hemagglutination tests on “transformed,” nontransformed, and primary cell cultures J. Natl. Cancer Inst. 1962 28 147 157 13872458
  5. [6]Gartler S.M. Genetic markers as tracers in cell culture Natl. Cancer Inst. Monogr. 1967 26 167 195 4864103
  6. [7]Nelson-Rees W.A. Flandermeyer R.R. Inter- and intraspecies contamination of human breast tumor cell lines HBC and BrCa5 and other cell cultures Science 1977 195 1343 1344 10.1126/science.557237 557237 · DOI
  7. [8]MacLeod R.A. Dirks W.G. Matsuo Y. Kaufmann M. Milch H. Drexler H.G. Widespread intraspecies cross-contamination of human tumor cell lines arising at source Int. J. Cancer 1999 83 555 563 10.1002/(SICI)1097-0215(19991112)83:4<555::AID-IJC19>3.0.CO;2-2 10508494 · DOI
  8. [9]Masters J.R. Thomson J.A. Daly-Burns B. Reid Y.A. Dirks W.G. Packer P. Toji L.H. Ohno T. Tanabe H. Arlett C.F. Short Tandem Repeat Profiling Provides an International Reference Standard for Human Cell Lines Proc. Natl. Acad. Sci. USA 2001 98 8012 8017 10.1073/pnas.121616198 11416159 PMC35459 · DOI · Paper page
  9. [14]Krishnamoorthy R.R. Clark A.F. Daudt D. Vishwanatha J.K. Yorio T. A forensic path to RGC-5 cell line identification: Lessons learned Investig. Ophthalmol. Vis. Sci. 2013 54 5712 5719 10.1167/iovs.13-12085 23975727 · DOI · Paper page
  10. [17]Vaughan L. Glänzel W. Korch C. Capes-Davis A. Widespread Use of Misidentified Cell Line KB (HeLa): Incorrect Attribution and Its Impact Revealed through Mining the Scientific Literature Cancer Res. 2017 77 2784 2788 10.1158/0008-5472.CAN-16-2258 28455420 · DOI · Paper page
  11. [19]Angeletti S. Matrix assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology J. Microbiol. Methods 2017 138 20 29 10.1016/j.mimet.2016.09.003 27613479 · DOI
  12. [20]Zhang X. Scalf M. Berggren T.W. Westphall M.S. Smith L.M. Identification of mammalian cell lines using MALDI-TOF and LC–ESI-MS/MS mass spectrometry J. Am. Soc. Mass Spectrom. 2006 17 490 499 10.1016/j.jasms.2005.12.007 16488154 · DOI
  13. [21]Marvin-Guy L.F. Duncan P. Wagnière S. Antille N. Porta N. Affolter M. Kussmann M. Rapid identification of differentiation markers from whole epithelial cells by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and statistical analysis Rapid Commun. Mass Spectrom. 2008 22 1099 1108 10.1002/rcm.3479 18335464 · DOI
  14. [22]Feng H.T. Wong N.S. Sim L.C. Wati L. Ho Y. Lee M.M. Rapid characterization of high/low producer CHO cells using matrix-assisted laser desorption/ionization time-of-flight Rapid Commun. Mass Spectrom. 2010 24 1226 1230 10.1002/rcm.4506 20391592 · DOI
  15. [23]Karger A. Bettin B. Lenk M. Mettenleiter T.C. Rapid characterisation of cell cultures by matrix-assisted laser desorption/ionisation mass spectrometric typing J. Virol. Methods 2010 164 116 121 10.1016/j.jviromet.2009.11.022 19941903 · DOI
  16. [24]Feng H.T. Sim L.C. Wan C. Wong N.S. Yang Y. Rapid characterization of protein productivity and production stability of CHO cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry Rapid Commun. Mass Spectrom. 2011 25 1407 1412 10.1002/rcm.5011 21504006 · DOI
  17. [25]Hanrieder J. Wicher G. Bergquist J. Andersson M. Fex-Svenningsen A. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue Anal. Bioanal. Chem. 2011 401 135 147 10.1007/s00216-011-5043-y 21553124 · DOI
  18. [26]Munteanu B. von Reitzenstein C. Hänsch G.M. Meyer B. Hopf C. Sensitive, robust and automated protein analysis of cell differentiation and of primary human blood cells by intact cell MALDI mass spectrometry biotyping Anal. Bioanal. Chem. 2012 404 2277 2286 10.1007/s00216-012-6357-0 22955673 · DOI
  19. [27]Munteanu B. Hopf C. Emergence of whole-cell MALDI-MS biotyping for high-throughput bioanalysis of mammalian cells? Bioanalysis 2013 5 885 893 10.4155/bio.13.47 23590472 · DOI
  20. [28]Ouedraogo R. Textoris J. Daumas A. Capo C. Mege J.L. Whole-cell MALDI-TOF mass spectrometry: A tool for immune cell analysis and characterization Methods Mol. Biol. 2013 1061 197 209 23963939
  21. [29]Povey J.F. O’Malley C.J. Root T. Martin E.B. Montague G.A. Feary M. Trim C. Lang D.A. Alldread R. Racher A.J. Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling J. Biotechnol. 2014 184 84 93 10.1016/j.jbiotec.2014.04.028 24858576 · DOI
  22. [30]Portevin D. Pflüger V. Otieno P. Brunisholz R. Vogel G. Daubenberger C. Quantitative whole-cell MALDI-TOF MS fingerprints distinguishes human monocyte sub-populations activated by distinct microbial ligands BMC Biotechnol. 2015 15 24 10.1186/s12896-015-0140-1 25887592 PMC4425930 · DOI
  23. [31]Juliano R.L. Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants Biochimica Biophysica Acta 1976 455 152 162 10.1016/0005-2736(76)90160-7 990323 · DOI
  24. [32]Cole S.P. Bhardwaj G. Gerlach J.H. Mackie J.E. Grant C.E. Almquist K.C. Stewart A.J. Kurz E.U. Duncan A.M. Deeley R.G. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line Science 1992 258 1650 1654 10.1126/science.1360704 1360704 · DOI · Paper page
  25. [33]Engelman J.A. Zejnullahu K. Mitsudomi T. Song Y. Hyland C. Park J.O. Lindeman N. Gale C.M. Zhao X. Christensen J. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling Science 2007 316 1039 1043 10.1126/science.1141478 17463250 · DOI · Paper page
  26. [34]Nazarian R. Shi H. Wang Q. Kong X. Koya R.C. Lee H. Chen Z. Lee M.K. Attar N. Sazegar H. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation Nature 2010 468 973 977 10.1038/nature09626 21107323 PMC3143360 · DOI
  27. [37]Poulikakos P.I. Persaud Y. Janakiraman M. Kong X. Ng C. Moriceau G. Shi H. Atefi M. Titz B. Gabay M.T. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E) Nature 2011 480 387 390 10.1038/nature10662 22113612 PMC3266695 · DOI · Paper page
  28. [38]Michaelis M. Rothweiler F. Barth S. Cinatl J. van Rikxoort M. Löschmann N. Voges Y. Breitling R. von Deimling A. Rödel F. Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells Cell Death Dis. 2011 2 243 10.1038/cddis.2011.129 PMC3252738 22170099 · DOI · Paper page
  29. [39]Michaelis M. Rothweiler F. Agha B. Barth S. Voges Y. Löschmann N. von Deimling A. Breitling R. Doerr H.W. Rödel F. Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents Cell Death Dis. 2012 3 e294 10.1038/cddis.2012.35 22476102 PMC3358013 · DOI
  30. [40]Domingo-Domenech J. Vidal S.J. Rodriguez-Bravo V. Castillo-Martin M. Quinn S.A. Rodriguez-Barrueco R. Bonal D.M. Charytonowicz E. Gladoun N. de la Iglesia-Vicente J. Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells Cancer Cell 2012 22 373 388 10.1016/j.ccr.2012.07.016 22975379 PMC5989708 · DOI
  31. [42]Joseph J.D. Lu N. Qian J. Sensintaffar J. Shao G. Brigham D. Moon M. Maneval E.C. Chen I. Darimont B. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509 Cancer Discov. 2013 3 1020 1029 10.1158/2159-8290.CD-13-0226 23779130 · DOI
  32. [43]Korpal M. Korn J.M. Gao X. Rakiec D.P. Ruddy D.A. Doshi S. Yuan J. Kovats S.G. Kim S. Cooke V.G. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide) Cancer Discov. 2013 3 1030 1043 10.1158/2159-8290.CD-13-0142 23842682 · DOI
  33. [44]Crystal A.S. Shaw A.T. Sequist L.V. Friboulet L. Niederst M.J. Lockerman E.L. Frias R.L. Gainor J.F. Amzallag A. Greninger P. Patient-derived models of acquired resistance can identify effective drug combinations for cancer Science 2014 346 1480 1486 10.1126/science.1254721 25394791 PMC4388482 · DOI · Paper page
  34. [45]Zahreddine H.A. Culjkovic-Kraljacic B. Assouline S. Gendron P. Romeo A.A. Morris S.J. Cormack G. Jaquith J.B. Cerchietti L. Cocolakis E. The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation Nature 2014 511 90 93 10.1038/nature13283 24870236 PMC4138053 · DOI
  35. [46]Hata A.N. Niederst M.J. Archibald H.L. Gomez-Caraballo M. Siddiqui F.M. Mulvey H.E. Maruvka Y.E. Ji F. Bhang H.E. Krishnamurthy Radhakrishna V. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition Nat. Med. 2016 22 262 269 10.1038/nm.4040 26828195 PMC4900892 · DOI · Paper page
  36. [47]Jung J. Lee J.S. Dickson M.A. Schwartz G.K. Le Cesne A. Varga A. Bahleda R. Wagner A.J. Choy E. de Jonge M.J. TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma Nat. Commun. 2016 7 12609 10.1038/ncomms12609 27576846 PMC5013668 · DOI
  37. [48]Göllner S. Oellerich T. Agrawal-Singh S. Schenk T. Klein H.U. Rohde C. Pabst C. Sauer T. Lerdrup M. Tavor S. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia Nat. Med. 2017 23 69 78 10.1038/nm.4247 27941792 PMC6548550 · DOI
  38. [49]Schneider C. Oellerich T. Baldauf H.M. Schwarz S.M. Thomas D. Flick R. Bohnenberger H. Kaderali L. Stegmann L. Cremer A. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia Nat. Med. 2017 23 250 255 10.1038/nm.4255 27991919 · DOI
  39. [50]Dirks W.G. Drexler H.G. STR DNA typing of human cell lines: Detection of intra- and interspecies cross-contamination Methods Mol. Biol. 2013 946 27 38 23179824
  40. [51]Oberthuer A. Skowron M. Spitz R. Kahlert Y. Westermann F. Mehler K. Berthold F. Fischer M. Characterization of a complex genomic alteration on chromosome 2p that leads to four alternatively spliced fusion transcripts in the neuroblastoma cell lines IMR-5, IMR-5/75 and IMR-32 Gene 2005 363 41 50 10.1016/j.gene.2005.07.038 16216448 · DOI
  41. [52]Cowell J.K. Chromosome abnormalities associated with salivary gland epithelial cell lines transformed in vitro and in vivo with evidence of a role for genetic imbalance in transformation Cancer Res. 1981 41 1508 1517 6260341
  42. [53]Honma M. Hayashi M. Ohno T. Mizusawa H. Saijo K. Sofuni T. Heterogeneity of the Y chromosome following long-term culture of the human lung cancer cell line A549 In Vitro Cell Dev. Biol. Anim. 1996 32 262 264 10.1007/BF02723057 8792154 · DOI · Paper page
  43. [54]Jackson-Cook C. Bae V. Edelman W. Brothman A. Ware J. Cytogenetic characterization of the human prostate cancer cell line P69SV40T and its novel tumorigenic sublines M2182 and M15 Cancer Genet. Cytogenet. 1996 87 14 23 10.1016/0165-4608(95)00232-4 8646734 · DOI
  44. [55]Sargent L. Dragan Y.P. Babcock K. Wiley J. Klaunig J. Pitot H.C. Cytogenetic analysis of three rat liver epithelial cell lines (WBneo, WBHa-ras, and WBrasIIa) and correlation of an early chromosomal alteration with insulin-like growth factor II expression Cancer Res. 1996 56 2992 2997 8674053
  45. [56]Weijerman P.C. van Drunen E. König J.J. Teubel W. Romijn J.C. Schröder F.H. Hagemeijer A. Specific cytogenetic aberrations in two novel human prostatic cell lines immortalized by human papillomavirus type 18 DNA Cancer Genet. Cytogenet. 1997 99 108 115 10.1016/S0165-4608(97)00207-0 9398864 · DOI
  46. [57]Park S.J. Jeong S.Y. Kim H.J. Y chromosome loss and other genomic alterations in hepatocellular carcinoma cell lines analyzed by CGH and CGH array Cancer Genet. Cytogenet. 2006 166 56 64 10.1016/j.cancergencyto.2005.08.022 16616112 · DOI
  47. [58]Lorenzi P.L. Reinhold W.C. Varma S. Hutchinson A.A. Pommier Y. Chanock S.J. Weinstein J.N. DNA fingerprinting of the NCI-60 cell line panel Mol. Cancer Ther. 2009 8 713 724 10.1158/1535-7163.MCT-08-0921 19372543 PMC4020356 · DOI · Paper page
  48. [59]Didion J.P. Buus R.J. Naghashfar Z. Threadgill D.W. Morse H.C. 3rd de Villena F.P. SNP array profiling of mouse cell lines identifies their strains of origin and reveals cross-contamination and widespread aneuploidy BMC Genom. 2014 15 847 10.1186/1471-2164-15-847 PMC4198738 25277546 · DOI · Paper page
  49. [60]Kotchetkov R. Driever P.H. Cinatl J. Michaelis M. Karaskova J. Blaheta R. Squire J.A. Von Deimling A. Moog J. Cinatl J. Jr. Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression Int. J. Oncol. 2005 27 1029 1037 10.3892/ijo.27.4.1029 16142320 · DOI
  50. [61]Michaelis M. Agha B. Rothweiler F. Löschmann N. Voges Y. Mittelbronn M. Starzetz T. Harter P.N. Abhari B.A. Fulda S. Identification of flubendazole as potential anti-neuroblastoma compound in a large cell line screen Sci. Rep. 2015 5 8202 10.1038/srep08202 25644037 PMC4314641 · DOI

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Authors
Povey, J. F., Saintas, E., Aderemi, A. V., Rothweiler, F., Zehner, R., Dirks, W. G., Cinatl, J., Racher, A. J., Wass, M. N., Smales, C. M., & Michaelis, M.
Affiliations
  • University of Kent (GB)
  • Goethe University Frankfurt (DE)
  • Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures (DE)
  • Lonza (United Kingdom) (GB)
Corresponding author
  • Smales, C. Mark
  • Michaelis, Martin
Venue
Cells
Publisher
MDPI AG
Published
2019-10-02
Volume
8
Issue
10
Pages
1194
ISSN
2073-4409 (ISSN-L)
OpenAlex
W2978807872
Cited by
5
References
11
Citations by year
2024: 1 · 2022: 2 · 2021: 1 · 2020: 1
FWCI
0.40
Type
journal article
Language
en
Open access
Locations
  • Cells (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kent Academic Repository (University of Kent) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/K017640/1)
  • Hilfe für krebskranke Kinder Frankfurt e.V. (n/a)
  • Frankfurter Stiftung für krebskranke Kinder (n/a)
  • Kent Cancer Trust (n/a)
  • Breast Cancer Kent (n/a)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Keywords
cell line authentication, neuroblastoma cell lines, cell line misidentification, cisplatin resistance, oxaliplatin resistance, vincristine resistance, vinblastine resistance, IMR-32
MeSH terms
Cell Line Authentication, Animals, Antineoplastic Agents, Cisplatin, Humans, Vincristine, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cell Line, Tumor

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